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1.
Banni S Angioni E Murru E Carta G Melis MP Bauman D Dong Y Ip C 《Nutrition and cancer》2001,41(1-2):91-97
The objective of this report was to determine whether vaccenic acid (t11-18:1) is converted efficiently to conjugated linoleic acid (c9,t11-18:2, CLA) in rats via the delta 9-desaturase reaction and, if so, whether vaccenic acid could substitute for CLA as an anticancer agent. In Study 1, rats were fed 1%, 2%, or 3% vaccenic acid in their diet, and tissue levels of CLA and CLA metabolites were determined in liver and mammary gland. In general, concentrations of CLA and CLA metabolites increased proportionately with an increase in vaccenic acid intake, at least up to the 2% dose level. Beyond this dose, there was clearly a plateauing effect. Thus vaccenic acid concentration increased from an undetectable level in the control to 78.5 nmol/mg lipid in the liver of rats fed a 2% vaccenic acid diet. This was accompanied by an increase in CLA from 2.3 to 33.6 nmol/mg lipid. These changes were also mirrored in the mammary gland, where increases in vaccenic acid (from 27.5 to 163.2 nmol/mg lipid) and CLA (from 17.8 to 108.9 nmol/mg lipid) were similarly observed. Vaccenic acid at 2% produced a CLA concentration in the mammary gland that was historically associated with a positive response in tumor inhibition based on our past experience. This provided the basis for selecting 2% vaccenic acid in Study 2, which was designed to evaluate its efficacy in blocking the development of premalignant lesions in the rat mammary gland. In this experiment, formation of histologically identifiable pathology due to intraductal proliferation of terminal end bud cells of mammary epithelium was used as the end point of analysis at 6 wk after carcinogen administration. Treatment with vaccenic acid reduced the total number of these premalignant lesions by approximately 50%. We hypothesize that the anticancer response to vaccenic acid is likely to be mediated by its endogenous conversion to CLA via delta 9-desaturase. 相似文献
2.
The anticarcinogenic effect of trans-11 18:1 is dependent on its conversion to cis-9, trans-11 CLA by delta9-desaturase in rats 总被引:2,自引:0,他引:2
The present study was designed to determine whether the ability of vaccenic acid (trans-11 18:1; VA) to reduce the risk of chemically induced mammary carcinogenesis in rats is direct or is mediated via conversion to cis-9, trans-11 conjugated linoleic acid (CLA). We previously reported that dietary VA caused a dose-dependent increase in the accumulation of CLA in the mammary fat pad, which was accompanied by a parallel decrease in the risk of mammary tumorigenesis. Specifically, our objective was to determine whether inhibiting Delta9-desaturase with cyclopropenoic fatty acids, supplied by sterculic oil (SO), would reverse the cancer-protective effect observed with a dietary supplement of VA-enriched butter. Female Sprague-Dawley rats were injected with a single dose of carcinogen (methylnitrosourea) and were fed 1 of 4 diets: 1) low VA (0.13% of diet), 2) low VA + SO (0.4% of diet), 3) high VA (1.60% of diet), and 4) high VA + SO. After 6 wk, the mammary glands were evaluated histologically for the appearance of premalignant lesions and were stained with bromodeoxyuridine to determine the extent of cell proliferation, and fatty acids were analyzed in plasma, liver, and mammary fat pad. The VA-enriched diet increased the tissue content of CLA, reduced the risk of developing premalignant lesions, and decreased the proliferative activity of premalignant cells in the mammary gland. Treatment with SO reversed the effects of VA. The anticarcinogenic effect of VA is predominantly, perhaps exclusively, mediated through its conversion to cis-9, trans-11 CLA via Delta9-desaturase, and when this conversion is blocked by SO, the biological response to VA is attenuated. 相似文献
3.
Conjugated linoleic acid isomers and mammary cancer prevention 总被引:10,自引:0,他引:10
Ip C Dong Y Ip MM Banni S Carta G Angioni E Murru E Spada S Melis MP Saebo A 《Nutrition and cancer》2002,43(1):52-58
There is increasing evidence that individual isomers of conjugated linoleic acid (CLA) may have unique biological or biochemical effects. A primary objective of this study was to determine whether there might be differences in the anticancer activity of 9,11-CLA and 10,12-CLA. This was achieved by evaluating the reduction in premalignant lesions and carcinomas in the mammary gland of rats that had been treated with a single dose of methylnitrosourea and given 0.5% of either highly purified CLA isomer in the diet. Our results showed that the anticancer efficacies of the two isomers were very similar. At 6 wk after carcinogen administration, the total number of premalignant lesions was reduced by 33-36%. At 24 wk, the total number of mammary carcinomas was reduced by 35-40%. The concentration of each CLA isomer and its respective metabolites was analyzed in the mammary fat pad. Tissue level of 10,12-CLA was much lower than that of 9,11-CLA. The pool of metabolites from each isomer was very similar between the two groups and represented only a small fraction of total conjugated diene fatty acids. Feeding of 9,11-CLA resulted in minimal changes in other unsaturated fatty acids. In contrast, feeding of 10,12-CLA produced a wider spectrum of perturbations. Small but significant increases in 16:1 and 16:2 were detected; these were accompanied by decreases in 20:2, 20:3, 20:4, 22:4, and 22:6. The above observation suggests that 10,12-CLA might be more potent than 9,11-CLA in interfering with elongation and desaturation of linoleic and linolenic acids. In summary, our study showed that, at the 0.5% dose level, the anticancer activity of 9,11-CLA and 10,12-CLA was very similar, even though accumulation of 10,12-CLA in the mammary tissue was considerably less than that of 9,11-CLA. These confounding changes of the other unsaturated fatty acids in contributing to the effect of 10,12-CLA need to be clarified. 相似文献
4.
Conjugated linoleic acid-enriched butter fat alters mammary gland morphogenesis and reduces cancer risk in rats 总被引:35,自引:0,他引:35
Ip C Banni S Angioni E Carta G McGinley J Thompson HJ Barbano D Bauman D 《The Journal of nutrition》1999,129(12):2135-2142
Conjugated linoleic acid (CLA) is a potent cancer preventive agent in animal models. To date, all of the in vivo work with CLA has been done with a commercial free fatty acid preparation containing a mixture of c9,t11-, t10,c12- and c11,t13-isomers, although CLA in food is predominantly (80-90%) the c9,t11-isomer present in triacylglycerols. The objective of this study was to determine whether a high CLA butter fat has biological activities similar to those of the mixture of free fatty acid CLA isomers. The following four different endpoints were evaluated in rat mammary gland: 1) digitized image analysis of epithelial mass in mammary whole mount; 2) terminal end bud (TEB) density; 3) proliferative activity of TEB cells as determined by proliferating cell nuclear antigen immunohistochemistry; and 4) mammary cancer prevention bioassay in the methylnitrosourea model. It should be noted that TEB cells are the target cells for mammary chemical carcinogenesis. Feeding butter fat CLA to rats during the time of pubescent mammary gland development reduced mammary epithelial mass by 22%, decreased the size of the TEB population by 30%, suppressed the proliferation of TEB cells by 30% and inhibited mammary tumor yield by 53% (P < 0.05). Furthermore, all of the above variables responded with the same magnitude of change to both butter fat CLA and the mixture of CLA isomers at the level of CLA (0.8%) present in the diet. Interestingly, there appeared to be some selectivity in the uptake or incorporation of c9,t11-CLA over t10,c12-CLA in the tissues of rats given the mixture of CLA isomers. Rats consuming the CLA-enriched butter fat also consistently accumulated more total CLA in the mammary gland and other tissues (four- to sixfold increases) compared with those consuming free fatty acid CLA (threefold increases) at the same dietary level of intake. We hypothesize that the availability of vaccenic acid (t11-18:1) in butter fat may serve as the precursor for the endogenous synthesis of CLA via the Delta9-desaturase reaction. Further studies will be conducted to investigate other attributes of this novel dairy product. 相似文献
5.
cis-9, trans-11 CLA derived endogenously from trans-11 18:1 reduces cancer risk in rats 总被引:6,自引:0,他引:6
The present study was designed to examine the effects of increasing dietary levels of vaccenic acid (VA) and cis-9, trans-11 conjugated linoleic acid (CLA) on chemically induced mammary carcinogenesis in rats. Both fatty acids were provided as a natural component in butter fat. The conversion of VA to CLA by delta9-desaturase was documented previously in several species, including rats and humans. Specifically, our objective was to determine the relative contribution of dietary VA and CLA to the tissue concentration of CLA and its ability to inhibit the development of mammary carcinomas. A total of 7 diets were formulated with varying levels of CLA and VA. The overall dietary treatment scheme was designed to evaluate the modulation of mammary cancer risk by 1). small increases of CLA in the presence of a low level of VA and 2). more substantial increases of VA against a background of low levels of CLA. As expected, small increases in dietary CLA at the low end of the CLA dose-response range did not reduce tumorigenesis. In contrast, there was a distinct and marked inhibitory response to VA that was dose dependent. The effect of VA was magnified in this experiment because the dose range of VA tested was much broader than that of CLA. Fatty acid analysis showed that the conversion of dietary VA to CLA resulted in a dose-dependent increase in the accumulation of CLA in the mammary fat pad, which was accompanied by a parallel decrease in tumor formation in the mammary gland. The finding confirms that the conversion of VA to CLA is as important for cancer prevention as the dietary supply of CLA. Thus, VA is also anticarcinogenic, and VA and CLA represent functional food components that are present in ruminant fat. 相似文献
6.
Ji-Na Lim Jin-Ju Oh Tao Wang Jae-Sung Lee Sang-Hun Kim Yoon-Jin Kim Hong-Gu Lee 《Nutrients》2014,6(2):627-636
Trans vaccenic acid (TVA; trans-11 18:1) is a positional and geometric isomer of oleic acid and it is the predominant trans isomer found in ruminant fats. TVA can be converted into cis-9, trans-11 conjugated linoleic acid (c9, t11-CLA), a CLA isomer that has many beneficial effects, by stearoyl CoA desaturase 1 (SCD1) in the mammary gland. The health benefits associated with CLA are well documented, but it is unclear whether trans fatty acids (TFAs) from ruminant products have healthy effects. Therefore, the effects of TVA on the proliferation of MCF-7 human breast adenocarcinoma cells and MCF-10A human breast epithelial cells were investigated in the present study. Results showed that TVA inhibited the proliferation of MCF-7 cells but not MCF-10A cells by down-regulating the expression of Bcl-2 as well as procaspase-9. In addition, the suppressive effect of TVA was confirmed in SCD1-depleted MCF-7 cells. Our results suggested that TVA exerts a direct anti-carcinogenic effect on MCF-7 cells. These findings provided a better understanding of the research on the anti-carcinogenic effects of TVA and this may facilitate the manufacture of TVA/c9, t11-CLA fortified ruminant products. 相似文献
7.
目的研究共轭亚油酸(CLA)对小鼠乳腺脂肪合成相关基因表达的影响。方法选取32只泌乳昆明鼠,随机分为对照组(2%花生油);0.5%CLA组(0.5%CLA+1.5%花生油);1.0%CLA组(1%CLA+1%花生油);1.5%CLA组(1.5%CLA+0.5%花生油),每组8只小鼠,从泌乳第4日饲喂至第14日,每日检测母鼠采食量、体重和仔鼠窝重,分析乳成分,采用荧光定量PCR检测对照组和1.5%CLA组母鼠乳腺组织脂肪合成相关基因的表达。结果在饲喂期间各组母鼠体重没有差异,饲料添加1.5%CLA显著减少了母鼠的采食量、仔鼠窝重和乳脂肪含量(P<0.05)。与对照组相比,1.5%CLA组母鼠乳腺组织的脂蛋白脂酶(LPL)、乙酰辅酶A羧化酶(ACACA)、硬脂酰辅酶A去饱和酶(SCD)和脂肪酸合成酶(FASN)的基因表达显著降低(P<0.05),并且转录因子固醇调节元件结合蛋白(SREBF)和过氧化物酶体增殖激活受体(PPARγ)的基因表达也显著下调(P<0.01)。结论饲料中加入1.5%CLA能够减少泌乳母鼠乳脂肪含量,抑制乳腺脂肪合成相关基因的表达。 相似文献
8.
9.
Recent studies showed that conjugated linoleic acids (CLA) lower triacylglycerol concentrations in the milk of lactating animals. This study was performed to determine the reasons for this phenomenon; we also investigated whether there is a relation between altered lipid metabolism in the liver and the reduction in milk triacylglycerols in rats fed CLA. Two groups of female rats were fed diets containing 0 [sunflower oil (SFO) group] or 14.7 g/kg diet of a CLA mixture (CLA group) at the expense of sunflower oil during growth, pregnancy, and lactation. CLA-fed rats had 49 and 80% lower mRNA concentration and activity of fatty acid synthase, respectively, a 51% lower mRNA concentration of lipoprotein lipase (LPL) in their mammary glands at d 17 of lactation, and a 46% lower milk fat content than SFO rats (P < 0.05). Although CLA rats had lower concentrations of triacylglycerols in the liver than SFO rats (20.8 +/- 2.6 vs. 62.6 +/- 27.7 micromol/g, P < 0.05), concentrations of triglycerides in plasma, which are the substrates of LPL, did not differ between the groups. Moreover, the number of pups per litter, litter weights, and pup weights at d 17 of lactation were 41, 35, and 22% lower, respectively, in the CLA group than in the SFO group. In conclusion, the present study suggests that dietary CLA reduces triacylglycerol concentrations in the milk via reduced de novo fatty acid synthesis in the mammary gland and an impaired uptake of fatty acids from lipoproteins into the mammary gland. This might be the reason for reduced growth rates and an increased mortality of suckling pups. 相似文献
10.
Shingfield KJ Ahvenjärvi S Toivonen V Vanhatalo A Huhtanen P 《The Journal of nutrition》2007,137(5):1154-1160
Cis-9, trans-11, the major isomer of conjugated linoleic acid (CLA) in bovine milk fat, is derived from ruminal biohydrogenation of 18:2 (n-6) and endogenous conversion of trans-11 18:1 (vaccenic acid; VA) in the mammary gland. Most evidence to date suggests that endogenous synthesis is the major source of cis-9, trans-11 CLA, but the extent of VA desaturation is less well defined. Four lactating cows were used in consecutive 4 x 4 Latin squares to examine changes in milk fatty acid composition and secretion in response to abomasal infusions of lipid supplements enriched with cis-9, trans-11 CLA (88.8%) or VA (29.4%). Treatments were infused over 4-d, followed by a 3-d washout, during 7 d experimental periods and administered to deliver 0, 3, 6, and 12 g cis-9, trans-11 CLA/d (Expt. 1) or 0, 7.5, 15 and 30 g VA/d (Expt. 2). Infusions of cis-9, trans-11 CLA increased linearly milk cis-9, trans-11 CLA concentrations from 0.68 to 1.46 g/100 g fatty acids. Abomasal infusions of VA increased linearly milk VA and cis-9, trans-11 CLA content from 1.22 to 2.72 and 0.61 to 1.24 g/100 g fatty acids, respectively. Changes in milk fatty acid secretion indicated that 28.9% of VA was converted to cis-9, trans-11 CLA. Results provide evidence that conversion by Delta9-desaturase to cis-9, trans-11 CLA in the lactating cow is independent of postruminal VA supply. In conclusion, endogenous synthesis via VA was equivalent to approximately 21% of the response to increases in cis-9, trans-11 CLA available for absorption. 相似文献
11.
《Nutrition and cancer》2013,65(2):233-238
Past research showed that mammary gland morphogenesis in the pubescent rat was retarded by the feeding of conjugated linoleic acid (CLA). A major objective of the present study was to examine the proliferative activity and the expression of cell cycle regulatory proteins in the developing mammary epithelium of rats fed a mixture of CLA isomers (primarily as free fatty acid c9,t11-CLA and t10,c12-CLA) or a highly enriched natural source of c9,t11-CLA (as triacylglycerol in butterfat). In both experiments, the diets, with or without CLA, were started at weaning and continued for four weeks. The two CLA preparations were equally effective in suppressing bromodeoxyuridine labeling and the expression of cyclin D1 and cyclin A (determined by immunohistochemistry) in the terminal end buds and alveolar clusters of the mammary epithelium while it undergoes extensive ductal branching during pubescence. There was a trend of an increase, although not statistically significant, in the proportion of cells expressing the p16 and p27 cdk inhibitors. A separate experiment was designed to evaluate the effect of c9,t11-CLA (as a free fatty acid of >90% purity) treatment on the rate of proliferation of the mammary epithelium as the animal matured from weanling to adult. The bromodeoxyuridine labeling data indicated that the mammary epithelium appeared to lose its sensitivity to CLA control of proliferation as it completely filled the fat pad and became quiescent. These observations suggest that the responsiveness of mammary epithelial cells to CLA intervention may be dependent on their proliferative status. 相似文献
12.
cis-9, trans-11 conjugated linoleic acid is synthesized directly from vaccenic acid in lactating dairy cattle 总被引:1,自引:0,他引:1
The utilization of (13)C-labeled vaccenic acid (VA) by lactating dairy cows to synthesize cis-9, trans-11 conjugated linoleic acid (CLA) was investigated. Primiparous ruminally cannulated Holstein cows (n = 3) were abomasally infused with 1.5 g of VA-1-(13)C. Blood and milk samples were taken frequently before and after VA infusion. Milk and plasma lipid were extracted using chloroform:methanol. Plasma lipid was separated into triacylglycerol (TG), cholesterol ester (CE), phospholipid (PL), nonesterified fatty acid (NEFA), and mono- and diacylglycerol (MDG) fractions. Lipid was methylated, converted to dimethyl disulfide and Diels-Alder adducts, and analyzed by GC-MS. Increased enrichment of (13)C was determined using a 2-sample t test for each sample time compared with -24 h, with significance declared at P < 0.05. Enrichment in milk fat VA was detected at 4 (3.0%), 8 (8.3%), 12 (4.1%), 16 (2.2%), and 20 h (0.8%). Enrichment in VA was also detected in plasma TG, NEFA, PL, and MDG. Enrichment in milk fat cis-9, trans-11 CLA, the Delta9-desaturase product of VA, was detected at 4 (2.6%), 8 (6.6%), 12 (3.4%), 16 (1.7%), and 24 h (0.7%). Enrichment was not detected in cis-9, trans-11 CLA for any plasma lipid fraction. Modeling of the data showed the exponential decay in (13)C enrichment over time for both VA and cis-9, trans-11 CLA in milk fat. Conversion of dietary VA to cis-9, trans-11 CLA endogenously was confirmed with the mammary gland being the primary site of Delta9-desaturase activity; approximately 80% of milk fat cis-9, trans-11 CLA originated from VA. 相似文献
13.
To investigate the effects of 2 conjugated linoleic acid (CLA) isomers and trans11-18:1 (TVA) on de novo lipogenesis and desaturation in liver and mammary gland, lactating mice were fed diets containing 3% canola oil (control) or 2% canola oil plus 1% stearic acid (SA), TVA, cis9,trans11 CLA (c9t11), or trans10,cis12 CLA (t10c12). In mammary tissue, TVA and CLA isomers reduced mRNA for acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) compared with control, but only c9t11 and t10c12 reduced mammary ACC activity. Of the 2 CLA isomers, t10c12 caused a greater reduction in mammary ACC activity. Hepatic ACC or FAS activity and mRNA abundance were not affected by dietary treatments. Feeding TVA, c9t11, or t10c12 reduced mammary stearoyl-CoA desaturase 1 (SCD) mRNA and activity. Reduction was greater due to feeding t10c12 compared with c9t11. Hepatic SCD mRNA was not affected by dietary treatments, but both CLA isomers depressed hepatic SCD activity. Results indicated that t10c12 is a more potent inhibitor of mammary lipogenesis and desaturation than is c9t11. A net gain of 77 and 1690 micro g of c9t11 in liver and mammary tissue, respectively, was found in the TVA-fed group over the control and SA-fed group. However, reduced mammary SCD mRNA or activity due to feeding TVA may indicate a limited capacity for desaturation of dietary TVA to c9t11 in vivo. 相似文献
14.
Inhibition of carcinogenesis by conjugated linoleic acid: potential mechanisms of action 总被引:14,自引:0,他引:14
Belury MA 《The Journal of nutrition》2002,132(10):2995-2998
Conjugated linoleic acid (CLA) is composed of positional and stereoisomers of octadecadienoate (18:2); it is found in foods derived from ruminants (beef and lamb as well as dairy products from these sources). When a mixture of isomers is fed to experimental animals, chemically induced tumorigenesis of mammary, skin and colon is reduced. Importantly, many isomers of CLA are readily metabolized to desaturated/elongated products as well as beta-oxidized products, suggesting that these metabolites may be important anticancer compounds. Mechanisms of inhibition of carcinogenesis may include reduction of cell proliferation, alterations in the components of the cell cycle and induction of apoptosis. In addition, CLA modulates markers of immunity and eicosanoid formation in numerous species as well as lipid metabolism and gene expression. It is likely that CLA exerts inhibitory properties in carcinogenesis via one or more of these pathways with some tissue specificity. This review will explore recent advances in putative mechanisms of reduction of carcinogenesis by CLA. 相似文献
15.
This study aimed to investigate the impact of management system and lactation stage on camel milk fatty acid (FA) composition, with emphasis on odd and branched-chain FA (OBCFA), conjugated linoleic acids (CLA), and trans-FA (TFA). Milk samples were collected from thirteen camels managed under intensive and semi-intensive systems at early, mid, and late lactation. Our results provided for the first time the OBCFA profile in camel milk. Eleven OBCFA were identified with a predominance of C15:0, anteiso-C15:0, anteiso-C17:0, and C17:0. The vaccenic acid (VA) was the predominant TFA; other isomers appeared in smaller amounts. The Δ9-desaturase activity measured as desaturation index of C14:0 was relatively high in the mammary gland of camel. Milk from the semi-intensive system was characterized by a higher nutritional value, due to the higher contents of total CLA, rumenic acid (RA), VA, linoleic, α-linolenic, and polyunsaturated FA compared with milk from the intensive system. Few differences were found in the OBCFA profile throughout lactation. Our study provided deeper information on FA composition, showing that camel milk is a good source of OBCFA, RA and VA. These results have to be taken into account in the investigation of the functional properties of camel milk fat as well as in the ongoing intensification of camel farming systems. 相似文献
16.
Meats cooked at high temperatures contain mutagenic heterocyclic amines such as 2‐amino‐l‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) and 2‐amino‐3‐methylimidazo[4,5‐f]quinoline (IQ). In female Fischer 344 rats, IQ is a multiorgan carcinogen, whereas PhIP induces mammary adenocarcinomas. For IQ and PhIP, N‐hydroxylation, catalyzed by microsomal cytochrome P‐450 1A1 and/or 1A2, and then esterification, especially O‐acetylation, are the principal steps leading to DNA adduct formation. Conjugated linoleic acid (CLA) is a mixture of conjugated linoleic acid isomers found in various meat and dairy products. We have examined the effect of dietary CLA on DNA adduct formation by PhIP and IQ in female Fischer 344 rats. Four‐week‐old animals were maintained on AIN‐76A diet without or with CLA (4% wt/wt) and treated with IQ or PhIP (50 mg/kg by gavage) after two weeks. Animals were killed (4/group) one, four, and eight days later. DNA isolated from mammary epithelial cells, liver, colon, and white blood cells was analyzed for carcinogen‐DNA adducts by 32P‐postla‐beling assays. On Day 1, dietary CLA significantly inhibited adduct formation (82.0%) in mammary epithelial cells in IQ‐but not in PhIP‐treated rats. In the colon, dietary CLA significantly inhibited PhIP‐DNA adduct formation (18.7%) on Day 8 but increased IQ‐DNA adduct formation (30.5%) on Day 8. Dietary CLA had no effect on adduct levels in liver or white blood cells. Calf thymus DNA was incubated with N‐hydroxy‐PhIP or ‐IQ in the presence of acetyl‐CoA. Enzymatic activation was catalyzed by liver or mammary cytosol. A two‐week pretreatment with 2% (wt/wt) dietary CLA had no effect on O‐acetyltransferase‐catalyzed IQ‐ or PhIP‐DNA adduct formation. It is concluded, under certain conditions, that dietary CLA can lower IQ‐ and PhlP‐DNA adduct formation. Overall, however, the major mode of action of CLA is probably by a mechanism other than the inhibition of the N‐hydroxylation and subsequent O‐acetylation of PhIP or IQ. 相似文献
17.
Agnieszka Stawarska Agnieszka Białek Ivana Stanimirova Tomasz Stawarski Andrzej Tokarz 《Nutrition and cancer》2013,65(1):145-155
The aim of the present research was to examine the effect of conjugated linoleic acids (CLA) supplementation on the activity of enzymes that take part in the synthesis of arachidonic acid (AA) and also to investigate the relation between their activity and the neoplastic process. The enzyme activities were established indirectly, because their measure was the amount of AA formed in vitro, being developed from linoleic acid as determined in liver microsomes of Spraque-Dawley rats. In addition, the indices of Δ6-desaturase (D6D) and Δ5-desaturase (D5D) were determined. To this aim, the method of high per-formance liquid chromatography with UV/VIS detection was used. Between the examined groups, statistically significant differences were observed in the activities of enzymes as well as D6D. The carcinogenic agent applied (DMBA) was found to significantly increase the activity of the examined enzymes. Negative correlation was found between the activities of desaturases and CLA supplementation, whereas the activity of those enzymes was a little higher in the group of rats with chemically induced cancer process. The neoplastic process has a stimulating effect on the activity of D6D. The decrease of D6D activity, resulting from the presence of CLA in the animals’ diet, may confirm the anticancer properties of these isomers. 相似文献
18.
Christina Donnelly Arne M. Olsen Lionel D. Lewis Burton L. Eisenberg Alan Eastman William B. Kinlaw 《Nutrition and cancer》2013,65(1):114-122
Spot 14 (THRSP, S14) is a nuclear protein involved in the regulation of genes required for fatty acid synthesis in normal and malignant mammary epithelial and adipose cells. Harvatine and Bauman (1) reported that conjugated linoleic acid (CLA) inhibits S14 gene expression in bovine mammary and mouse adipose tissues and reduces milk fat production in cows. We hypothesized that CLA inhibits S14 gene expression in human breast cancer and liposarcoma cells and that this will retard their growth. Exposure of T47D breast cancer cells to a mixture of CLA isomers reduced the expression of the S14 and fatty acid synthase (FAS) genes. The mixture caused a dose-related inhibition of T47D cell growth, as did pure c9, t11 and t10, c12-CLA, but not linoleic acid. Similar effects were observed in MDA-MB-231 breast cancer cells. Provision of 8 μM palmitate fully (CLA mix, t10, c12-CLA) or partially (c9, t11-CLA) reversed the antiproliferative effect in T47D cells. CLA likewise suppressed levels of S14 and FAS mRNAs in liposarcoma cells and caused growth inhibition that was prevented by palmitic acid. CLA did not affect the growth of nonlipogenic HeLa cells or human fibroblasts. We conclude that as in bovine mammary and mouse adipose cells, CLA suppresses S14 and FAS gene expression in human breast cancer and liposarcoma cells. Rescue from the antiproliferative effect of CLA by palmitic acid indicates that reduced tumor lipogenesis is a major mechanism for the anticancer effects of CLA 相似文献
19.
Conjugated linoleic acid (CLA) is a potent inhibitor of the initiation and promotion of mammary carcinogenesis in animal models, but its role in colon carcinogenesis remains unclear. The objective of this study was to determine whether CLA inhibits the promotion of colon carcinogenesis. Forty male Sprague-Dawley rats were given a single dose of azoxymethane (20 mg/kg body wt ip). After 1 wk, the animals were randomized into two groups (n = 20) and fed a control AIN-93G diet or the control diet supplemented with 1% CLA at the expense of the soybean oil. After 12 wk, the animals were killed, and their colons were stained with methylene blue for aberrant crypt foci (ACF) analysis by light microscopy. The total number of ACF per animal did not differ between the control (174 ±11) and CLA (170 ± 10) groups. Furthermore, CLA did not affect the average crypt multiplicity (crypts/ACF) or the average number of ACF in any size category. However, rats fed the 1% CLA diet had significantly higher serum insulin levels at the time of sacrifice than those fed the control diet. Thus it is possible that the promoting effects of elevated serum insulin on colon carcinogenesis may have counteracted an inhibitory effect of CLA. 相似文献
20.
Past research showed that mammary gland morphogenesis in the pubescent rat was retarded by the feeding of conjugated linoleic acid (CLA). A major objective of the present study was to examine the proliferative activity and the expression of cell cycle regulatory proteins in the developing mammary epithelium of rats fed a mixture of CLA isomers (primarily as free fatty acid c9, t11-CLA and t10,c12-CLA) or a highly enriched natural source of c9,t11-CLA (as triacylglycerol in butterfat). In both experiments, the diets, with or without CLA, were started at weaning and continued for four weeks. The two CLA preparations were equally effective in suppressing bromodeoxyuridine labeling and the expression of cyclin D1 and cyclin A (determined by immunohistochemistry) in the terminal end buds and alveolar clusters of the mammary epithelium while it undergoes extensive ductal branching during pubescence. There was a trend of an increase, although not statistically significant, in the proportion of cells expressing the p16 and p27 cdk inhibitors. A separate experiment was designed to evaluate the effect of c9,t11-CLA (as a free fatty acid of > 90% purity) treatment on the rate of proliferation of the mammary epithelium as the animal matured from weanling to adult. The bromodeoxyuridine labeling data indicated that the mammary epithelium appeared to lose its sensitivity to CLA control of proliferation as it completely filled the fat pad and became quiescent. These observations suggest that the responsiveness of mammary epithelial cells to CLA intervention may be dependent on their proliferative status. 相似文献